Yes we can! Successful examples of disallowing ‘conscientious objection’ in reproductive health care

Reproductive health care is the only field in medicine where health care professionals (HCPs) are allowed to limit a patient’s access to a legal medical treatment – usually abortion or contraception?– by citing their ‘freedom of conscience.’ However, the authors’ position is that ‘conscientious objection’ (‘CO’) in reproductive health care should be called dishonourable disobedience because it violates medical ethics and the right to lawful health care, and should therefore be disallowed. Three countries – Sweden, Finland, and Iceland – do not generally permit HCPs in the public health care system to refuse to perform a legal medical service for reasons of ‘CO’ when the service is part of their professional duties. The purpose of investigating the laws and experiences of these countries was to show that disallowing ‘CO’ is workable and beneficial. It facilitates good access to reproductive health services because it reduces barriers and delays. Other benefits include the prioritisation of evidence-based medicine, rational arguments, and democratic laws over faith-based refusals. Most notably, disallowing ‘CO’ protects women’s basic human rights, avoiding both discrimination and harms to health. Finally, holding HCPs accountable for their professional obligations to patients does not result in negative impacts. Almost all HCPs and medical students in Sweden, Finland, and Iceland who object to abortion or contraception are able to find work in another field of medicine. The key to successfully disallowing ‘CO’ is a country’s strong prior acceptance of women’s civil rights, including their right to health care.     

Very Long-term Outcomes and Predictors of Percutaneous Coronary Intervention with Drug-eluting Stents Versus Coronary Artery Bypass Grafting for Patients with Unprotected Left Main Coronary Artery Disease

Background:

There are limited data on longer-term outcomes (>5 years) for patients with unprotected left main coronary artery (ULMCA) disease who underwent percutaneous coronary intervention (PCI) in the drug-eluting stents (DES) era. This study aimed at comparing the long-term (>5 years) outcomes of patients with ULMCA disease underwent PCI with DES and coronary artery bypass grafting (CABG) and the predictors of adverse events.

Methods:

All consecutive patients with ULMCA disease treated with DES implantation versus CABG in our center, between January 2003 and July 2009, were screened for analyzing. A propensity score analysis was carried out to adjust for potential confounding between the two groups.

Results:

Nine hundred and twenty-two patients with ULMCA disease were enrolled for the analyses (DES = 465 vs. CABG = 457). During the median follow-up of 7.1 years (interquartile range 5.3–8.2 years), no difference was found between PCI and CABG in the occurrence of death (P = 0.282) and the composite endpoint of cardiac death, myocardial infarction (MI) and stroke (P = 0.294). Rates of major adverse cardiac and cerebrovascular events were significantly higher in the PCI group (P = 0.014) in large part because of the significantly higher rate of repeat revascularization (P < 0.001). PCI was correlated with the lower occurrence of stroke (P = 0.004). Multivariate analysis showed ejection fraction (EF) (P = 0.012), creatinine (P = 0.016), and prior stroke (P = 0.031) were independent predictors of the composite endpoint of cardiac death, MI, and stroke in the DES group, while age (P = 0.026) and EF (P = 0.002) were independent predictors in the CABG group.

Conclusions:

During a median follow-up of 7.1 years, there was no difference in the rate of death between PCI with DES implantation and CABG in ULMCA lesions in the patient cohort. CABG group was observed to have significantly lower rates of repeat revascularization but higher stroke rates compared with PCI. EF, creatinine, and prior stroke were independent predictors of the composite endpoint of cardiac death, MI, and stroke in the DES group, while age and EF were independent predictors in the CABG group.     

MicroRNA-539靶向膜相关的鸟苷酸激酶蛋白1抑制甲状腺癌细胞的侵袭与迁移

目的 观察microRNA-539（miR-539）的表达对甲状腺癌细胞侵袭与迁移的影响,探究miR-539与膜相关的鸟苷酸激酶蛋白1（CARMA1）在甲状腺癌中相互作用的机制。方法 构建miR-539与CARMA1高表达及低表达的细胞模型后通过transwell及MTT法检测两种不同的甲状腺癌细胞的侵袭、迁移及增殖能力。Western blot及RT-PCR检测细胞中蛋白及mRNA表达。结果  miR-539抑制甲状腺癌细胞的侵袭与迁移。通过荧光素酶报告检测发现miR-539通过靶向CARMA1的3’-UTR端从而起到抑制甲状腺癌中CARMA1的作用。进一步的研究证实,CARMA1可显著促进甲状腺癌细胞的侵袭与迁移。而调节CARMA1的表达,miR-539随之变化。研究还发现,与对照组比较,甲状腺癌中miR-539的表达量降低而CARMA1的表达量增加。结论  miR-539靶向CARMA1抑制甲状腺癌细胞的侵袭与迁移。

     

老年患者发生迟发性脑缺血前多种影响因素的探究

目的  探究老年患者发生迟发性脑缺血（DCI）的危险因素,防止迟发性脑缺血的发生。方法  回顾性分析120例动脉瘤性蛛网膜下腔出血患者。年龄60～79岁,Fisher分级>1。将患者分为DCI组和非DCI组。分析患者的相关指标（性别、吸烟史、局部脑氧饱和度等）,找出迟发性脑缺血的独立危险因素,并用受试者工作曲线评估其预测性能。结果  所有入组患者中,69例患者伴有DCI。单因素分析结果表明,DCI组患者中,有吸烟史、低钠、局部脑氧饱和度<50的患者比例明显大于非DCI组,差异有统计学意义（P <0.05）。多因素Logistic回归分析发现,钠离子浓度（■=3.011,95%CI：1.123,8.070）与局部脑氧饱和度（■=3.324,95%CI：1.734,6.372）是迟发性脑缺血的独立危险因素,且局部脑氧饱和度预测性能更佳。结论  局部脑氧饱和度是老年患者动脉瘤性蛛网膜下腔出血后迟发性脑缺血较好的预测指标。

     

人类非嗜肝病毒所致肝炎患者临床特征的相关性分析

目的  探讨人类非嗜肝病毒所致肝炎的病因和临床特征。方法  对176例人类非嗜肝病毒性肝炎患者进行临床研究,用常规方法检测112例甲-戊型肝炎标志物,排除嗜肝病毒感染。检测单纯疱疹病毒（HSV）、EB病毒（EBV）、巨细胞病毒（CMV）、柯萨奇病毒（CoxV）等病毒的IgM、IgG型抗体和自身抗体（线粒体抗体和抗核抗体）,随访6个月,并将其临床症状体征、肝功能指标与同期急性病毒性肝炎比较。结果  非嗜肝病毒肝炎患者病原体以CMV感染最多（34.7%）,其次分别为EB病毒和轮状病毒感染（24.4%、9.6%）,非嗜肝病毒肝炎患者的乏力、纳差、厌油、恶心、肝肿大、皮肤黄染发生率较同期急性病毒性肝炎低,两者比较差异有统计学意义（P <0.01）,其脾肿大、淋巴结肿大的发生率较同期急性病毒性肝炎高,两者比较差异有统计学意义（P <0.01）;非嗜肝病毒肝炎患者肝功能的ALT、AST、TBIL值较同期的急性病毒性肝炎值低,两者比较差异有统计学意义（P <0.01）,清蛋白、凝血酶原时间值与急性病毒性肝炎比较,差异无统计学意义（P > 0.05）;非嗜肝病毒肝炎患者的单一感染的ALT、AST、TBIL较复合感染时间短,两者比较差异有统计学意义（P <0.01）。结论  巨细胞病毒、EB病毒等为非嗜肝病毒肝炎的常见病原体,临床表现为急性肝损伤,但较急性病毒性肝炎轻,单一感染较复合感染轻,预后较好。

     

Dexamethasone treatment modulates aquaporin-4 expression after intracerebral hemorrhage in rats

This study investigated whether dexamethasone (DEX) treatment could regulate the expression of aquaporin-4 (AQP4) in rats with intracerebral hemorrhage (ICH). The results demonstrated that DEX significantly reduced AQP4 mRNA level in the perihematomal area compared with control group, but it increased the level in the brain area surrounding the third ventricle at day 1 post-ICH. There was no difference in AQP4 protein levels between DEX group and control group at the two above-mentioned brain regions at day 1 after ICH. The changes in AQP4 protein induced by DEX were marked at day 3 following surgery and still lasted at day 5 post-ICH, which were accompanied by a reduction of brain edema. Our results demonstrated that the expression of AQP4 protein after ICH was region-specific, time-dependent, and also indicated that DEX-induced cerebral edema clearance was correlated with the regulation of AQP4 expression in different brain regions.     

Meiotic segregation analysis in spermatozoa of pericentric inversion carriers using fluorescence in-situ hybridization

BACKGROUND: Pericentric inversions are structural chromosomal abnormalities resulting from two breaks, one on either side of the centromere, within the same chromosome, followed by 180 degrees rotation and reunion of the inverted segment. They can perturb spermatogenesis and lead to the production of unbalanced gametes through the formation of an inversion loop. METHODS: We report here the analysis of the meiotic segregation in spermatozoa from six pericentric inversion carriers by multicolour fluorescence in-situ hybridization (FISH) and review the literature. RESULTS: The frequencies of the non-recombinant products (inversion or normal chromosomes) were 80% for the inv(20), 91.41% for the inv(12), 99.43% for the inv(2), 68.12% for the inv(1), 97% for the inv(8)(p12q21) and 60.94% for the inv(8)(p12q24.1). The meiotic segregation of 20 pericentric inversions (including ours) is now available. The frequency of unbalanced spermatozoa varies from 0 to 37.85%. The probability of a crossover within the inverted segment is affected by the chromosome and region involved, the length of the inverted segment and the location of the breakpoints. CONCLUSIONS: No recombinant chromosomes were produced when the inverted segment involved <30% of the chromosome length (independent of the size of the inverted segment). Between 30 and 50%, few recombinant chromosomes were produced, inducing a slightly increased risk of aneusomy of recombination in the offspring. The risk of aneusomy became very important when the inverted segment was >50% of the chromosome length. Studies on spermatozoa from inversion carriers help in the comprehension of the mechanisms of meiotic segregation. They should be integrated in the genetic exploration of the infertile men to give them a personalized risk assessment of unbalanced spermatozoa.     

Effect of pH and Metal Ions on the Decomposition Rate of <Emphasis Type="Italic">S</Emphasis>-nitrosocysteine

S-nitrosothiols (RSNOs) have many biological functions including platelet deactivation, immunosupression, neurotransmission, and host defense. Most of the functions are attributed to nitric oxide (NO) release during S-nitrosothiol decomposition. As the simplest biologically occurring S-nitrosothiol, S-nitrosocysteine (CySNO) has been widely used as an NO donor and has also been incorporated into biomedical polymers. Knowledge of the CySNO decomposition rate is important for assessing the impact of CySNO on various bioengineering applications or biological systems. In this work, spectrophotometer measurements of CySNO decomposition in the presence of metal ions showed that the decomposition rate is highly susceptible to the pH. The maximum decomposition occurs near physiological pH (near 7.4) while in the acidic (pH < 6) and alkaline (pH > 9) condition CySNO is very stable. This demonstrates that blood provides an optimized environment for the decomposition of CySNO leading to the release of NO. The CySNO decomposition rate can also be affected by buffers with different purity levels in the presence and absence of metal ion chelators—although all buffers show the same pH phenomenon of maximizing near physiological pH. An equilibrium model of metal ions as a function of pH provides a plausible explanation for the pH dependence on the experimental decomposition rate.     

Differential regulation of interleukin-1 receptor associated kinase 1 (IRAK1) splice variants

IRAK family proteins play critical roles in regulating innate immunity. There are three differentially spliced variants of IRAK1, namely 1, 1b, and 1c. We and others have previously identified that the full length IRAK1 underwent covalent modifications such as phosphorylation and ubiquitination upon lipopolysaccharide challenge. In this report, we observed that IRAK1 could also undergo sumoylation which was responsible for its translocation into the nucleus. In contrast, IRAK1c remained stable and did not undergo modification upon various challenges. Furthermore, we showed that IRAK1c solely localized in the cytoplasm. IRAK1 was absent and IRAK1c was the primary form in human brains. The absence of full length IRAK1 and presence of IRAK1c may keep brain tissue in a resting non-inflammatory state. Intriguingly, the full length IRAK1 form was consistently detected in brain tissues obtained from aged humans, suggesting that differential splicing of IRAK1 may correlate with the aging process.     

HLA-associated genetic resistance and susceptibility to type I diabetes in French North Africans and French natives

The distribution of human leukocyte antigen (HLA)-DRB1-DQA1-DQB1 haplotypes was analyzed separately in two distinct French ethnic groups with type I diabetes (T1D), i.e. French North African migrants (n= 64, mean age at diagnosis = 8.25 years) and ancient French natives (n= 60, mean age at diagnosis = 7.42 years). HLA associations were determined by calculating odds ratios (ORs) between patients and two ethnic-matched control populations. Results show highly similar ORs for the conservative DRB1*0301-DQA1*0501-DQB1*0201 haplotype of susceptibility (OR: 3.22 and 3.93 in migrants and natives, respectively) and the DRB1*1501-DQA1*0102-DQB1*0602 haplotype of resistance (OR: 0.05 and 0.03, respectively). In contrast, among the more variable DRB1*04-DQB1*0302 haplotypes of susceptibility, the DRB1*0402 (OR: 3.10 and 32.84) and 0405 (OR: 5.90 and 16.25, respectively) were associated with T1D in migrants and natives, whereas an increase of DRB1*0401, a rare allele in migrants, was significant in natives only. Also, among the DRB1*11-DQA1*0505-DQB1*0301 haplotypes of resistance, the OR observed for DRB1*1104-DQA1*0505-DQB1*0301, common in migrants, was lower (OR: 0.08) than for DRB1*1101-DQA1*0505-DQB1*0301 (OR: 0.32), common in natives. How DRB1*11 subtypes might affect differently the risk conferred by DQA1*0505-DQB1*0301 will be discussed.